Plasmatic L-AScorbic Acid in MYelodyplastic Syndroms and Controls

NCT ID: NCT02809222

Last Updated: 2021-04-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-25

Study Completion Date

2021-03-01

Brief Summary

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Myelodysplastic syndromes (MDS) is a group of heterogeneous diseases characterised by the clonal evolution of dysplastic hematopoietic stem cells. This evolution is associated with accumulation of cytogenetic mutations which leads to acute myeloid leukaemia (AML). Evolution of MDS is also associated with increase of reactive oxygen species (ROS). The increase of ROS is associated with accumulation of cytogenetic mutations. Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body.

Studies showed that supplementation with AA can change the proliferation status of MDS cells. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients with myelodysplastic syndromes advanced in their treatment or recently diagnosed during a follow-up of 12 months.

Detailed Description

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Myelodysplastic syndromes (MDS) is a group of heterogeneous life threatening diseases characterised by the clonal evolution of dysplastic myeloid hematopoietic stem cells. This evolution is initially associated with an excess of apoptosis followed by an excess of proliferation then, after accumulation of cytogenetic mutations, a transformation in acute myeloid leukaemia (AML) can appear. Evolution of MDS is also associated with increase of reactive oxygen species (ROS) . In MDS mice, perturbations of the metabolism of ROS is associated with increases in the number of cytogenetic mutations.

Ascorbic acid (AA) is an actor of the regulation of the oxidative metabolism in the human body. In vitro studies showed that supplementation with AA can change the proliferation status of MDS cells . Guinea pigs with a phenotype with excess of ROS supplemented with AA have less somatic mutations and less MDS. Adjuvant treatment with AA is associated with a beneficial effect on the evolution of MDS and AML.

To our knowledge no study have demonstrated the variations of the parameters of the oxidative metabolism during the evolution of MDS. The present study aim at describing the variations of plasmatic ascorbic acid concentrations between healthy volunteers and patients diagnosed with MDS in treatment or recently diagnosed during a follow-up of 12 months. During the follow-up a collection of plasma from volunteers and patients will be created for later analysis.

Conditions

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Myelodysplastic Syndrome Secondary Acute Myeloid Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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Patients with MDS at diagnosis

The intervention, specific to the study, is to take blood samples on patients with MDS at diagnosis. A quality of life questionnaire will also be used to monitor patients

Group Type OTHER

Samples

Intervention Type OTHER

Blood samples

Quality of life questionnaire

Intervention Type OTHER

Questionnaire to assess the quality of life of cancer patients

Patients with MDS in treatment

The intervention, specific to the study, is to take blood samples on patients with MDS receiving treatment. A quality of life questionnaire will also be used to monitor patients

Group Type OTHER

Samples

Intervention Type OTHER

Blood samples

Quality of life questionnaire

Intervention Type OTHER

Questionnaire to assess the quality of life of cancer patients

Healthy volunteers

The intervention, specific to the study, is to take blood samples on patients healthy volunteers.

Group Type OTHER

Samples

Intervention Type OTHER

Blood samples

Interventions

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Samples

Blood samples

Intervention Type OTHER

Quality of life questionnaire

Questionnaire to assess the quality of life of cancer patients

Intervention Type OTHER

Other Intervention Names

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EORTC QLQ-C30

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification
* Patient diagnosed for less than 4 months before inclusion
* Patient untreated by other means than blood transfusions
* Age ≥ 60 years
* Patient affiliated to social security scheme
* Informed consent signed by the patient

* Diagnosis of myelodysplastic syndrome according to the 2008 WHO classification
* Patient not included in patients MDS "at diagnosis" group
* Patient diagnosed for more than 12 months
* Treated with hypomethylating agents and/or erythropoiesis-stimulating agents and/or blood transfusions.
* Age ≥ 60 years
* Patient affiliated to social security scheme
* Informed consent signed by the patient


* Age ≥ 60 years
* Patient affiliated to social security scheme
* Informed consent signed by the patient

Exclusion Criteria

* Previous allogenic stem cell transplantation
* Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
* Active inflammatory disease
* Patient under legal protection measure
* Patient unwilling or who cannot submit to prospective biological follow-up
2. Patients MDS "in treatment" group selection criteria:

* Previous allogenic stem cell transplantation
* Patient with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
* Active inflammatory disease
* Patient under legal protection measure
* Patient unwilling or who cannot submit to prospective biological follow-up
3. Healthy volunteers group selection criteria:


* History of another primary malignancy that is currently clinically significant or currently requires active intervention
* History of active inflammatory diseases
* Volunteer under legal protection measure
* Volunteer unwilling or who cannot submit to prospective biological follow-up
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Tours Autogreffe

UNKNOWN

Sponsor Role collaborator

Novartis

INDUSTRY

Sponsor Role collaborator

University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emmanuel GYAN, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Tours

Locations

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Clinical Research Center, University Hospital, Tours

Tours, , France

Site Status

Department of Haematology and Cell Therapy, University Hospital, Tours

Tours, , France

Site Status

Countries

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France

References

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Das A, Dey N, Ghosh A, Das T, Chatterjee IB. NAD(P)H: quinone oxidoreductase 1 deficiency conjoint with marginal vitamin C deficiency causes cigarette smoke induced myelodysplastic syndromes. PLoS One. 2011;6(5):e20590. doi: 10.1371/journal.pone.0020590. Epub 2011 May 31.

Reference Type BACKGROUND
PMID: 21655231 (View on PubMed)

Ghoti H, Amer J, Winder A, Rachmilewitz E, Fibach E. Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome. Eur J Haematol. 2007 Dec;79(6):463-7. doi: 10.1111/j.1600-0609.2007.00972.x. Epub 2007 Nov 1.

Reference Type BACKGROUND
PMID: 17976187 (View on PubMed)

Hole PS, Darley RL, Tonks A. Do reactive oxygen species play a role in myeloid leukemias? Blood. 2011 Jun 2;117(22):5816-26. doi: 10.1182/blood-2011-01-326025. Epub 2011 Mar 11.

Reference Type BACKGROUND
PMID: 21398578 (View on PubMed)

Chung YJ, Robert C, Gough SM, Rassool FV, Aplan PD. Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome. Leuk Res. 2014 Jan;38(1):95-102. doi: 10.1016/j.leukres.2013.07.008. Epub 2013 Aug 16.

Reference Type BACKGROUND
PMID: 23958061 (View on PubMed)

Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999 Apr 21;281(15):1415-23. doi: 10.1001/jama.281.15.1415.

Reference Type BACKGROUND
PMID: 10217058 (View on PubMed)

Park CH. Vitamin C in leukemia and preleukemia cell growth. Prog Clin Biol Res. 1988;259:321-30.

Reference Type BACKGROUND
PMID: 3362876 (View on PubMed)

Park CH, Kimler BF. Growth modulation of human leukemic, preleukemic, and myeloma progenitor cells by L-ascorbic acid. Am J Clin Nutr. 1991 Dec;54(6 Suppl):1241S-1246S. doi: 10.1093/ajcn/54.6.1241s.

Reference Type BACKGROUND
PMID: 1962577 (View on PubMed)

Park CH, Kimler BF, Bodensteiner D, Lynch SR, Hassanein RS. In vitro growth modulation by L-ascorbic acid of colony-forming cells from bone marrow of patients with myelodysplastic syndromes. Cancer Res. 1992 Aug 15;52(16):4458-66.

Reference Type BACKGROUND
PMID: 1643638 (View on PubMed)

Park CH, Kimler BF, Yi SY, Park SH, Kim K, Jung CW, Kim SH, Lee ER, Rha M, Kim S, Park MH, Lee SJ, Park HK, Lee MH, Yoon SS, Min YH, Kim BS, Kim JA, Kim WS. Depletion of L-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes. Eur J Haematol. 2009 Aug;83(2):108-18. doi: 10.1111/j.1600-0609.2009.01252.x. Epub 2009 Mar 5.

Reference Type BACKGROUND
PMID: 19284416 (View on PubMed)

Parker JE, Fishlock KL, Mijovic A, Czepulkowski B, Pagliuca A, Mufti GJ. 'Low-risk' myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro- versus anti-apoptotic bcl-2-related proteins. Br J Haematol. 1998 Dec;103(4):1075-82. doi: 10.1046/j.1365-2141.1998.01114.x.

Reference Type BACKGROUND
PMID: 9886323 (View on PubMed)

Parker JE, Mufti GJ, Rasool F, Mijovic A, Devereux S, Pagliuca A. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood. 2000 Dec 1;96(12):3932-8.

Reference Type BACKGROUND
PMID: 11090080 (View on PubMed)

Saito N, Miyamoto M, Gotoh U, Yoshitomi S. Effect of biscoclaurine alkaloids, prednisolone and ascorbic acid on myelodysplastic syndrome with pancytopenia: a case report. Eur J Haematol. 2000 Jan;64(1):61-5. doi: 10.1034/j.1600-0609.2000.9l036.x. No abstract available.

Reference Type BACKGROUND
PMID: 10680708 (View on PubMed)

Welch JS, Klco JM, Gao F, Procknow E, Uy GL, Stockerl-Goldstein KE, Abboud CN, Westervelt P, DiPersio JF, Hassan A, Cashen AF, Vij R. Combination decitabine, arsenic trioxide, and ascorbic acid for the treatment of myelodysplastic syndrome and acute myeloid leukemia: a phase I study. Am J Hematol. 2011 Sep;86(9):796-800. doi: 10.1002/ajh.22092. Epub 2011 Aug 3. No abstract available.

Reference Type BACKGROUND
PMID: 21815182 (View on PubMed)

Other Identifiers

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2016-A00539-42

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHAO16-EG/PLASMYC

Identifier Type: -

Identifier Source: org_study_id

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